{"doi":"10.1101/2024.11.29.625575","title":"Cutaneous human papillomavirus E6 impairs the cGAS-STING pathway","abstract":"Beta genus human papillomaviruses (β-HPVs) are ubiquitous double stranded DNA (dsDNA) viruses that may promote skin cancers by destabilizing the host genome. Supporting this, expression of the E6 gene from a β-HPV (β-HPV 8 E6) results in increased micronuclei that should induce an innate immune response that eliminates these cells. Yet, β-HPV 8 E6 promotes rather than restricts proliferation. We hypothesize that β-HPV 8 E6 accomplishes this by attenuating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, an innate immune pathway that becomes activated in response to cytosolic micronuclear dsDNA. Here, we show that in response to stimulation by transfection of pLVX-GFP plasmid, β-HPV 8 E6 reduced the magnitude and intensity of cGAS-STING pathway activation in immunoblot experiments. These data also demonstrate that impairment of the cGAS-STING pathway is strongest downstream of STING phosphorylation. Further, RNA-sequencing suggests that β-HPV 8 E6 downregulates other innate immune pathways. We also show that cGAS is recruited to micronuclei induced by β-HPV 8 E6. These data suggest a mechanism by which β-HPV 8 E6 facilitates proliferation of cells destabilized by micronuclei and support the hypothesis that the prevalence of β-HPV infections is in part due to the impairment of the cGAS-STING innate immune response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486470,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":751488,"name":"Dalton Dacus","orcid":"0000-0001-9588-5048","position":1,"is_corresponding":false},{"id":1330700,"name":"Rose Pollina","orcid":null,"position":2,"is_corresponding":false},{"id":383910,"name":"Nicholas A. Wallace","orcid":"0000-0002-3971-716X","position":3,"is_corresponding":false},{"id":748949,"name":"Emily Tolbert","orcid":null,"position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"39677810","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}